1. Field of the Invention
The invention relates to the generation of water cluster ions (hydronium clusters) at atmospheric pressure for the chemical ionization of analyte molecules in a mass spectrometer.
2. Description of the Related Art
In this document, the term “hydronium” refers to the cation H3O+. The literature is somewhat inconsistent in that this cation is sometimes called simply “hydronium”, but the term “hydronium ion” is also used. The complexes with further water molecules are called “hydronium clusters” here; these are always positively charged.
Atmospheric pressure chemical ionization (APCI) usually takes place in an ionization chamber in which a corona discharge burns at a metal tip due to the application of a high voltage of several kilovolts. The analyte molecules which are to be ionized are introduced into the ionization chamber. The corona discharge usually burns in a nitrogen atmosphere, creating nitrogen ions primarily. Hydronium clusters of the form [H(H2O)n]+ are created from the nitrogen ions on a microsecond time scale due to water being unavoidably present in at least ppm concentrations. These clusters are able to ionize the analyte molecules by means of a subsequent complex proton transfer. In equilibrium at room temperature and ambient pressure, the hydronium clusters have a broad distribution of cluster size n, mainly with 3<n<9, where the protonation force of the clusters is very small for large n due to low acidity; for very small n the protonation force is large due to high acidity. The distribution of the cluster size depends on the local pressure and the local temperature, but also on the distance from the metal tip and the concentration of the water since, initially, the hydronium (H3O+) is formed near the tip, but surrounds itself with further water molecules as it migrates away from the tip to the outside. The lower the water concentration, the further to the outside the cluster formation takes place, and the larger is the space in which an analyte molecule of a specific proton affinity can be ionized. In order to maintain uniform ionization of analyte molecules for quantitative analyses, it is necessary to have good control of the water concentration.
Chemical ionization by hydronium clusters is a complex process which does not consist simply of a proton transfer to the analyte molecule, but can also run through phases where an analyte molecule combines with a hydronium cluster with subsequent loss of neutral water molecules. The intermediate stages can be understood as protonated analyte ions with a solvate sheath. The water molecules can leave the complex if the analyte molecule has a sufficiently high internal temperature. The release of the water molecules causes the internal temperature to fall. The removal of the solvate sheath (“desolvation”) can be assisted in the known way by collisions with ambient gas, which cause heating. In this way it is possible, to a lesser extent, to also ionize analyte molecules of lower proton affinity with larger hydronium clusters, i.e. of higher proton affinity, although this is not energetically possible by the direct route of a proton transfer.
In order to facilitate the protonation, however, it may be appropriate to first decompose the hydronium clusters by collisional heating so that, most importantly, the H3O+ and H5O2+ ions are again available for the protonation. The collisional heating consists in drawing the hydronium cluster ions through a suitable gas with the aid of an electric drawing field at a suitable pressure so that they absorb energy from a large number of collisions. This technique has led to a separate type of mass spectrometry which is called PTR-MS and is used especially to measure organic trace impurities in ambient air (PTR=proton transfer reaction). PTR is understood more restrictively to be a special type of chemical ionization where hydronium clusters are reduced in size by heating collisions, such as in a linear drift tube, thus making it possible to also quantitatively ionize low-molecular substances of relatively low proton affinity. In PTR-MS, the hydronium clusters are produced by hollow cathode discharges at low pressures of water being fed in.
Outside of the specialized PTR-MS, there are two designs of APCl ion sources for mass spectrometers of a more general type. In the first design, the analyte molecules are introduced in a gas, for example from a gas chromatograph. The molecules are usually relatively small, vaporizable analyte molecules with molecular masses below 500 daltons. The feeding gas is essentially dry, with a water content of a few ppm (parts per million) to a few hundred ppm. Since the proton affinities of these analyte molecules are usually not very high, the aim is to keep the hydronium clusters as small as possible, i.e., to maintain a low yet constant water concentration in the ionization chamber with the corona discharge. This is difficult. Moreover, the corona discharge has a tendency to also form reactive compounds, such as ozone O3 and OH radicals, which can lead to oxidative changes of the analyte molecules. Furthermore, some of the analyte ions always decompose in the corona discharge, which leads to undesirable fragment ions in the mass spectra. It is therefore advantageous to spatially separate the formation of the reactant ions and the chemical ionization of the analyte molecules, as has already been proposed in the patent specification DE 10 2009 037 716 B4 (T. Benter et al.; corresponding to US 2011/0039350 A1 and GB 2 473 106 A).
The second type of APCI ion source is designed to ionize analyte molecules which are brought into the gas phase by spraying, for example thermospraying or spraying by a gas jet, via the drying of the spray droplets. This also includes the post-ionization of analyte molecules which are not at all ionized in electrospray ion sources, or only to a small extent. Electrospray ion sources are used mainly for the ionization of biological macromolecules such as peptides and proteins. These can generally be protonated efficiently. There are exceptions, however, which can be post-ionized by Cl. Such a post-ionization is described in US 2008/0173809 A1, for example. Since the spray liquids usually contain water, there is a high concentration of water in the ionization chamber; but the usually chaotic gas flows and gas vortices in the ionization chamber do not produce a well-controlled chemical ionization.
In view of the foregoing, there is a need to produce hydronium clusters in a simple, stable and well-controlled way with the facility to adjust the size distribution of the clusters so that they can be effectively used as reactant ions for the chemical ionization of analyte molecules.